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April 7, 2004

Inhaled Nitric Oxide for Acute Lung Injury: No Place for NO?

Author Affiliations

Author Affiliations: Departments of Critical Care Medicine and Medicine, Sunnybrook and Women's College Health Sciences Centre (Dr Adhikari) and Department of Medicine, University Health Network, Faculty of Medicine, University of Toronto (Dr Granton), Toronto, Ontario.

JAMA. 2004;291(13):1629-1631. doi:10.1001/jama.291.13.1629

It is estimated that up to 107 000 cases of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) occur yearly in the United States.1 Although the mortality rate from ARDS has been decreasing, between 17 000 and 43 000 patients die from ALI and ARDS annually.2 Despite substantial progress in understanding the pathophysiology of this syndrome and numerous randomized controlled trials (RCTs) of both pharmacological agents and mechanical ventilatory strategies, the only interventions shown to reduce mortality have been lung-protective strategies of mechanical ventilation that decreased tidal volume.3-5 In the ARDS Network trial, tidal volume limitation was associated with a clinically and statistically significant 22% relative reduction in mortality for patients with ALI and ARDS.4 Central to the success of these trials is the concept that mechanical ventilation itself perpetuates lung injury. Although this concept has led to positive studies of interventions to decrease iatrogenic lung damage complicating ARDS, no multicenter trial has convincingly demonstrated benefit from interventions such as surfactants, corticosteroids, ketoconazole, or other therapies that treat the underlying pathogenic mechanisms or physiological perturbations that characterize ALI and ARDS.3